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A Review of Immunosenescence – Article by Steve Hill

A Review of Immunosenescence – Article by Steve Hill

Steve Hill

Editor’s Note: In this article, Steve Hill discusses some of the reasons for the decline of the immune system.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 9, 2018

Immunosenescence is the age-related decline of the immune system. The reason why our immune systems start to fail and weaken as we age is not fully understood, and, indeed, there are a variety of hypotheses as to why this happens.


Inflammation certainly plays a role in this process, and it is well documented that inflammation has a considerable effect on immune cells such as macrophages, causing them to become dysfunctional and stop cleaning house. This is in line with the proposed concept of “inflammaging”, which describes an ever-increasing chronic background of inflammation from sources such as senescent cells, cell debris, and changes in the gut microbiota. This inflammaging then drives immune system dysfunction, which then creates more inflammation, continuing a downward spiral.

We recently learned that inflammation can cause problems with weight control by causing nerve-associated macrophages to stop signaling fat cells to release their stored energy[1]. We also know that macrophage dysfunction occurs in other tissues due to inflammation, and so it seems clear that inflammation plays at least a partial role in immune system decline.

Cellular Senescence

Some research suggests that the immune system declines due to its cells becoming senescent, just as other cell populations do. Over time, our cells reach their maximum number of divisions, or they are damaged and enter senescence and destroy themselves via apoptosis, a kind of programmed self-destruct sequence.

However, sometimes these cells resist apoptosis and cling on to life, but in doing so, they prevent fresh cells replacing them while generating inflammatory signals that cause nearby cells to become dysfunctional, too. It is proposed that the immune system experiences the same senescence as our other cells, leading to immune system failure.

Stem-cell depletion

Another player in immune system decline is stem-cell depletion; for example, the thymus begins to shrink from an early age and eventually stops producing new T cells to help defend us from invading pathogens. The production of T cells is facilitated by thymic stem cells, which are gradually depleted over our lifetime, and eventually, we have so few T cells that we cannot fight off diseases such as flu and pneumonia, which often kill the elderly. Some attempts are currently being made to rejuvenate the thymus and have enjoyed some success.

A review of immunosenescence

It is likely the case that immunosenescence is a combination of all of these proposed things and more, and each plays a role in the resulting decline of our immune systems as we age. When it comes to establishing the exact chain of events that leads to immunosenescence, it will take reversing each of those causes to see what happens.

Today, we wanted to bring your attention to an open-access paper that reviews the current knowledge of immunosenescence and provides a good introduction to the topic[2].


Developing the therapies that target the aging processes directly is likely the most expedient path to understanding immunosenescence, as these therapies will give us the tools with which to discover what drives the process. Approaches such as thymic rejuvenation or creating a replacement thymus, replacing lost stem-cell populations such as hematopoietic stem cells that create all immune cells, removing overspecialized immune cells, and removing senescent cells are all valid approaches towards discovering how immunosenescence works.

Our knowledge is growing rapidly by the passing month, and more and more is being understood about the aging processes and how we might directly target them to prevent or reverse age-related diseases. It is almost certain that medicine is going to change dramatically in the next decade or two as our understanding grows.


[1] Camell, C. D., Sander, J., Spadaro, O., Lee, A., Nguyen, K. Y., Wing, A., … & Rodeheffer, M. S. (2017). Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature, 550(7674), 119-123.

[2] Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clinical and Molecular Allergy, 15(1), 21.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).


In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.